Abstract

Rationale

A number of studies have associated reduced Akt1 expression with vulnerability for schizophrenia. Although mice with deletion of a single copy of the Akt1 gene (Akt1+/−) show reduced Akt1 expression relative to wild-type (WT) animals, the extent to which these mice show schizophrenia-like phenotypic changes and/or increased susceptibility to epigenetic or non-genetic factors related to schizophrenia is unknown.

Objectives

Mutant mice were assessed on electroencephalographic/event-related potential (EEG/ERP) and behavioral (acoustic startle and pre-pulse inhibition) measures relevant to schizophrenia. Mice were also assessed following exposure to the NMDA receptor antagonist ketamine, a potent psychotomimetic drug, in order to assess the role of reduced Akt1 expression as a vulnerability factor for schizophrenia. Methods Akt1+/−, Akt1−/−, and WT mice received a series of paired-click, white noise stimuli, following ketamine (50 mg/kg) and saline injections. EEG was analyzed for ERPs and event-related power. Akt1+/− and WT mice were also assessed on PPI following ketamine (50 mg/kg) or saline injection.

Results

Akt1+/− and Akt1−/− mice displayed reduced amplitude of the P20 component of the ERP to the first click of a paired-click stimulus, as well as reduced S1–S2 difference for P20 and N40 components, following ketamine. Mutant mice also showed increased reduction in gamma synchrony and theta suppression following ketamine. Akt1+/− mice displayed reduced pre-pulse inhibition.

Conclusions

Reduced genetic expression of Akt1 facilitated ketamine-induced changes of EEG and behavior in mice, suggesting that reduced Akt1 expression can serve as a vulnerability factor for schizophrenia.